Cancer is a genetic disease of single cell origin caused by the accumulation of inherited and acquired mutations in specific cancer genes, which have normal cellular functions, but when mutated or present at abnormally high levels contribute to cancer. One type of mutation is gene amplification or overexpression, i.e., where a specific chromosomal region (including the cancer gene) has undergone a relative increase in DNA copy number, such that more copies of the cancer gene are present, or where the level of expression of a gene is increased, such that a correspondingly higher amount of mRNA and protein is produced, causing deleterious effects. Gene amplification is one of the primary genetic alterations in solid tumors, and most of the chromosomal regions that undergo amplification are not well characterized and do not harbor known oncogenes (Knuutila et al., Am. J. Pathol. 152:1107–23 (1998); Knuutila et al., Cancer Genet. Cytogenet. 100:25–30 (1998)). Discovery of these amplified cancer genes will provide novel targets for diagnostic and therapeutic applications.
The present invention is based on the discovery that Pellino gene, polynucleotide, and polypeptide sequences are amplified and/or overexpressed in cancer cells in mammals. As described herein, this discovery has provided new diagnostic, prognostic, and therapeutic methods for the treatment of cancer, in particular for ovarian and lung cancer.